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Abstract

Dengue virus (DENV) is a single stranded RNA virus principally transmitted by the Aedes aegypti mosquito. There is currently no widely used vaccine or cure available for those infected with dengue virus. Vector control methods remain the gold standard strategy for blocking disease transmission. Unfortunately, none of the environmental, chemical or biological mosquito control methods that are currently being employed in endemic regions have had success in curtailing the breadth of dengue transmission. As such, novel dengue control strategies are in urgent need. To begin to address this issue, we have focused on approaches to block the pathogen in the mosquito, and for this a thorough understanding of how dengue virus infection is modulated in the mosquito is required. Studies have shown that complex interactions between the mosquito’s innate immune response, its microbiota and the ingested pathogens are critical determinants of the outcome of pathogen infection. During dengue virus extrinsic incubation period, viral replication in the mosquito midgut results in the activation of immune signaling pathways that produce the mosquito’s antiviral effectors. In our previous studies, we isolated two dengue virus restriction factors (DVRF), DVRF1 and DVRF2, which represent putative downstream effectors of the JAK-STAT immune signaling pathway, and have been proven to exert anti-dengue activity. However, little is known about how these putative effector molecules mediate their anti-dengue effect. We have begun to address this question by elucidating the extent to which DVRF1 and DVRF2 are implicated in the defense against bacterial infections.
As previously mentioned, the interaction between the mosquito’s innate immune response, its microbiota and the ingested pathogens are critical determinants of the outcome of pathogen infection. So, understanding how the microbial component influences mosquito-pathogen interactions is critical. We have shown that a field-derived fungus increases the susceptibility of the Aedes aegypti mosquitoes to dengue virus infection. We have suggested a mechanism through which this effect is being mediated, and have also initiated an effort of screening additional mosquito- gut associated fungi for their effects on dengue virus susceptibility. A deeper understanding of the factors that influence the resistance of Aedes aegypti mosquitoes to dengue virus infections could possibly result in new strategies to control disease transmission.